Clinical Neuroscience

[LGI1 encephalitis: the first Hungarian patient]

SZŐTS Mónika, MARTON Annamária, ILLÉS Zsolt, BAJZIK Gábor, NAGY Ferenc

JULY 30, 2015

Clinical Neuroscience - 2015;68(07-08)


[In the recent years, it has been increasingly recognised that in a group of limbic encephalitis antibodies are directed against the scaffolding protein LGI1 (Leucine-rich glioma inactivated 1), which is part of the voltage gated potassium channel (VGKC) complex on neural synapses. Patients present with seizures and subacute history of neuropsychiatric symptoms, including psychosis and changes in memory, cognition, behaviour. Faciobrachial dystonic seizures can be observed, which are highly characteristic for LGI1 encephalitis. MRI shows medial temporal abnormalities in more than half of the cases. CSF evaluation is usually normal. Hyponatremia is frequently associated and may confuse the initial diagnosis. Early recognition and prompt initiation of immunotherapies are of great importance. The clinical improvements often correlate with the antibody levels. We present the case of a 64-year old man, who responded quickly to plasma exchange and major improvement was noted within few weeks.]



Further articles in this publication

Clinical Neuroscience

Thrombocytopenia with gabapentin usage

ATAKLI Dilek, YUKSEL Burcu, AK Dogan Pelin, SARIAHMETOGLU Hande, SARI Hüseyin

Gabapentin is an antiepileptic drug approved for adjunctive therapy for partial seizures. We report a case of a patient who had thrombocytopenia with the dose of 2400 mg/day of gabapentin. The causal relationship between gabapentin and thrombocytopenia was revealed by dramatic increase in thrombocyte count following the cessation of the gabapentin treatment. To our knowledge, this is the first case report with a hematopoietic side effect of gabapentin.

Clinical Neuroscience

Mental health of physicians - nationwide representative study from Hungary


Background and aim - Somatic and mental health and stress factors of physicians became an issue of growing interest in both national and international researches. Our aim is to give an overviewing analysis of Hungarian physicians’ mental health state. Methods - Representative, cross-sectional, quantitative survey on a representative sample of Hungarian physicians (n=4784). The control group was formed by the population group of a national survey conducted by “Hungarostudy 2013” (n=2000). Results - Suicidal thoughts (18.8% vs. 9.6%, p<0.001), the scores of Somatic Symptom Scale (PHQ-10, 20.4% vs. 13.6%, p<0.001) were significantly higher among physicians. The suicidal attempts (1.9% vs. 3.5%, p=0.053) and BDI depression scores (7.9% vs. 29.5%, p<0.001) were significantly higher in the control group. High Perceived Stress Scale (PPS) scores occurred in 43.3% of the physicians sample, and 43.4% of them had high scores in the Athenian Insomnia Scale (AIS). The young (<35) female physicians showed significantly higher rates of suicidal thoughts, higher scores of PHQ and PPS. In the young female cohort, the AIS scores were significantly higher than of the other physicians. Conclusions - Mental health of physicians (sleep disorders, suicidal thoughts and psychosomatic symptoms) showed poorer results than the population data. BDI scores and the rate of suicidal attempts showed favourable trends. The next step in the physicians’ mental health researches is to investigate the most decisive risk factors, and to work out the prevention tools.

Clinical Neuroscience

[Focal motor seizures and status epilepticus provoked by mirtazapine]


[The seizure-provoking effect of the tetracyclic antidepressant mirtazapine is not a well-known adverse effect of the drug. The authors report on a 39-year-old non-epileptic patient who had been treated for depression with the usual daily dose of mirtazapine. Having increased the daily dose of the drug from 30 to 45 milligrams he experienced a few clonic seizures of the right lower limb. This symptom and insomnia erroneously intended the patient to further increase the daily dose of mirtazapine, which immediately resulted in the evolution of focal clonic status epilepticus in the same limb. After admission, this condition was recorded by video-EEG and abolished by intravenous administration of levetiracetam after the intravenous clonazepam had been ineffective. Discontinuation of mirtazapine and administration of carbamazepine resulted in completely seizure-free state that persisted even after carbamazepine treatment was terminated. The clinical and laboratory data indicate the seizure-provoking effect of mirtazapine in the reported case.]

Clinical Neuroscience

[The role of β-amyloid and mitochondrial dysfunction in the pathogenesis of Alzheimer’s disease]


[Alzheimer’s disease is the most common form of dementia in mid- and late life. The 7-10% of the population over 65 and the 50-60% of the population over 85 are affected by this disease. On the contrary of its prevalence the pathogenesis of the disease is not well defined and there is no effective neuroprotective therapeutic agent. Three predominant neuropathological features of the Alzheimer’s disease brain are intracellular neurofibrillary tangles consisting mainly of the hyperphosphorylated protein t; the extracellular amyloid deposits (neuritic plaques) consisting of amyloid b peptide; and the extensive neuronal cell loss in the hippocampus and in portions of the cerebral cortex. The possible reason of the extensive neuronal cell loss can be the mitochondrial dysfunction observed in Alzheimer’s disease. Beyond the unclarified pathogenesis the causality of these characteristic neuropathologic phenomena are still unknown. In this study we would like to deal with two actual hypotheses, with the amyloid cascade and with the mitochondrial cascade hypotheses. We try to give an overview of these two hypotheses and to depict their interrelationship.]

Clinical Neuroscience

[Radiosurgery of intracerebral cavernomas - Current Hungarian practice]

FEDORCSÁK Imre, NAGY Gábor, DOBAI József Gábor, MEZEY Géza, BOGNÁR László

[Background and purpose - Radiosurgery is an increasingly popular treatment option especially for deep eloquent intracerebral cavernomas that are often too risky for surgical removal, but their re-bleed carries significant risk for persisting neurological deficit. Gamma-radiation based radiosurgery has been being available since 2007 in Hungary in Debrecen. Our aim is to summarize our experience accumulated during the first five years of treatment and to compare it to the international experience. Patient selection and methods - We retrospectively analyzed 51 cavernomas in 45 patients treated between 2008 and 2012 in terms of localization, natural history, and the effect of radiosurgery on re-bleed risk and epilepsy, and its side effects. Results - We treated 26.5% deep eloquent (brainstem, thalamic/basal ganglia) and 72.5% superficial hemispheric cavernomas. The median presentation age was 25 years (13-60) for deep, and 45 years (6-67) for superficial cavernomas. They were treated median of 1 year after presentation. 64.5% of deep cavernomas bled before treatment, the annual risk of first hemorrhage was 2%/lesion, re-bleed risk 21.7%, with 44% persisting morbidity. 13.5% of superficial cavernomas bled prior to treatment, the risk of first bleed was 0.3%, there was no re-bleed, and 35% caused epilepsy. We used GammaART-6000TM rotating gamma system for treatment, marginal dose was 14 Gy (10-16), and treatment volume 1.38-1.53 cm3. Re-bleed risk of deep eloquent lesions fell to 4% during the first two years after treatment and to 0% thereafter, and no hemorrhage occurred from superficial lesions after treatment. Persisting morbidity in deep lesions came from adverse radiation effect in 7% and from re-bleed in 7%, and there was no persisting side effect in superficial cavernomas. 87.5% of cases of epilepsy resistant to medical therapy improved. Radiological regression was found in 37.5% and progression in 2% after treatment. Conclusions - Radiosurgery of cavernomas is safe and effective. Early preventive treatment for deep cavernomas carrying high surgical risk is justified. Moreover, for superficial lesions that are surgically easily accessible radiosurgery also appears to be an attractive alternative.]

All articles in the issue

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Clinical Neuroscience

Neuroscience highlights: Main cell types underlying memory and spatial navigation

KRABOTH Zoltán, KÁLMÁN Bernadette

Interest in the hippocampal formation and its role in navigation and memory arose in the second part of the 20th century, at least in part due to the curious case of Henry G. Molaison, who underwent brain surgery for intractable epilepsy. The temporal association observed between the removal of his entorhinal cortex along with a significant part of hippocampus and the developing severe memory deficit inspired scientists to focus on these regions. The subsequent discovery of the so-called place cells in the hippocampus launched the description of many other functional cell types and neuronal networks throughout the Papez-circuit that has a key role in memory processes and spatial information coding (speed, head direction, border, grid, object-vector etc). Each of these cell types has its own unique characteristics, and together they form the so-called “Brain GPS”. The aim of this short survey is to highlight for practicing neurologists the types of cells and neuronal networks that represent the anatomical substrates and physiological correlates of pathological entities affecting the limbic system, especially in the temporal lobe. For that purpose, we survey early discoveries along with the most relevant neuroscience observations from the recent literature. By this brief survey, we highlight main cell types in the hippocampal formation, and describe their roles in spatial navigation and memory processes. In recent decades, an array of new and functionally unique neuron types has been recognized in the hippocampal formation, but likely more remain to be discovered. For a better understanding of the heterogeneous presentations of neurological disorders affecting this anatomical region, insights into the constantly evolving neuroscience behind may be helpful. The public health consequences of diseases that affect memory and spatial navigation are high, and grow as the population ages, prompting scientist to focus on further exploring this brain region.

Clinical Neuroscience

Management of bone metabolism in epilepsy

UÇAN TOKUÇ Ezgi Firdevs , FATMA Genç, ABIDIN Erdal, YASEMIN Biçer Gömceli

Many systemic problems arise due to the side effects of antiepileptic drugs (AEDs) used in epilepsy patients. Among these adverse effects are low bone mineral density and increased fracture risk due to long-term AED use. Although various studies have supported this association with increased risk in recent years, the length of this process has not been precisely defined and there is no clear consensus on bone density scanning, intervals of screening, and the subject of calcium and vitamin D supplementation. In this study, in accordance with the most current recommendations, our applications and data, including the detection of possible bone mineralization disorders, treatment methods, and recommendations to prevent bone mineralization disorders, were evaluated in epilepsy patients who were followed up at our outpatient clinic. It was aimed to draw attention to the significance of management of bone metabolism carried out with appropriate protocols. Epilepsy patients were followed up at the Antalya Training and Research Hospital Department of Neurology, Epilepsy Outpatient Clinic who were at high risk for osteoporosis (use of valproic acid [VPA] and enzyme-inducing drugs, using any AED for over 5 years, and postmenopausal women) and were evaluated using a screening protocol. According to this protocol, a total of 190 patients suspected of osteoporosis risk were retrospectively evaluated. Four patients were excluded from the study due to secondary osteoporosis. Of the 186 patients who were included in the study, 97 (52.2%) were women and 89 (47.8%) were men. Prevalence of low bone mineral density (BMD) was 42%, in which osteoporosis was detected in 11.8% and osteopenia in 30.6% of the patients. Osteoporosis rate was higher at the young age group (18-45) and this difference was statistically significant (p=0.018). There was no significant difference between male and female sexes according to osteoporosis and osteopenia rates. Patients receiving polytherapy had higher osteoporosis rate and lower BMD compared to patients receiving monotherapy. Comparison of separate drug groups according to osteoporosis rate revealed that osteoporosis rate was highest in patient groups using VPA+ carbamazepine (CBZ) (29.4%) and VPA polytherapy (19.4%). Total of osteopenia and osteoporosis, or low BMD, was highest in VPA polytherapy (VPA+ non-enzyme-inducing AED [NEID]) and CBZ polytherapy (CBZ+NEID) groups, with rates of 58.3% and 55.1%, respectively. In addition, there was no significant difference between drug groups according to bone metabolism markers, vitamin D levels, and osteopenia-osteoporosis rates. Assuming bone health will be affected at an early age in epilepsy patients, providing lifestyle and diet recommendations, avoiding polytherapy including VPA and CBZ when possible, and evaluating bone metabolism at regular intervals are actions that should be applied in routine practice.

Clinical Neuroscience

Effects of valproate, carbamazepine and levetiracetam on Tp-e interval, Tp-e/QT and Tp-e/QTc ratio


Aim - To evaluate P-wave dispersion before and after antiepileptic drug (AED) treatment as well as to investigate the risk of ventricular repolarization using the Tpeak-Tend (Tp-e) interval and Tp-e/QT ratio in patients with epileptic disorder. Methods - A total of 63 patients receiving AED therapy and 35 healthy adults were included. ECG recordings were obtained before and 3 months after anti-epileptic treatment among patients with epilepsy. For both groups, Tp-e and Tp-e/QT ratio were measured using a 12-lead ECG device. Results - Tp-e interval, Tpe/QT and Tp-e/QTc ratios were found to be higher in the patient group than in the control group (p<0.05, for all), while QTmax ratio was significantly lower in the patient group. After 3 months of AED therapy, significant increases in QT max, QTc max, QTcd, Tp-e, Tp-e/QT, and Tp-e/QTc were found among the patients (p<0.05). When the arrhythmic effects of the drugs before and after treatment were compared, especially in the valproic acid group, there were significant increases in Tp-e interval, Tp-e/QT and Tp-e/QTc values after three months of treatment (p<0.05). Carbamazepine and levetiracetam groups were not statistically significant in terms of pre- and post-treatment values. Conclusions - It was concluded that an arrhythmogenic environment may be associated with the disease, and patients who received AED monotherapy may need to be followed up more closely for arrhythmia.

Clinical Neuroscience

[Personalised epilepsy treatment]


[Epilepsy is one of the most common chronic neurological disease in childhood. Patients with epilepsy – even with so-called benign epilepsy – need medication for years. During this time, children go through a very big change, not only gaining weight and height, but also changing hormonal and metabolic processes. Maturation processes in different brain areas also take place at different rates depending on age. All of these should be considered when preparing a therapeutic plan. In everyday practice after the diagnosis of epilepsy, the applied drug is most often selected based on the shape and type of seizure. However, a number of other factors need to be considered when designing a therapeutic strategy: 1. efficacy (form of epilepsy, type of seizure), 2. age, gender, 3. pharmacological properties of the drug, 4. adverse drug reaction profile, 5. lifestyle (community), figure (skinny, corpulent, obese), 6. other comorbidities (nutrition, behavioral and learning problems, circulatory disorders, kidney or liver disease), 7. expected interactions with other drugs already used, 8. genetics, 9. other aspects (drug registration and prescription rules). The purpose of this article is to help to decide which antiepileptic drugs are expected to have the least side effects in a particular child with different comorbidities and which medications should be avoided if possible.]

Lege Artis Medicinae

[Epilepsy in coronavirus pandemic]


[We aim to review the impact of COVID-19 pandemic on epilepsy and epilepsy-care. While the virus has no specific link with epilepsy, it may affect the nervous system both directly and indirectly, leading to seizures in several ways. The hyper-coagulable state occurring with the infection may cause strokes leading to seizures. The infection may first manifest in the form of disturbances of consciousness and behaviour, seizures, and even status epilepticus. The interactions of antiviral/antiepileptic drugs need to be taken into account during treatment. The hypercoagulable state induced by COVID-2 infection may cause stroke, which leads to seizures. The infection can occur also as an impaired consciousness of non-epileptic origin. Interactions of antiviral/antiepileptic drugs have also to be taken into account. The pandemic itself as well as quarantines and social distancing may cause anxiety and insomnia, challenge continuous antiepileptic supply; each one carrying the risk of seizing. Young epilepsy patients with learning disabilities and mental health issues are most vulnerable, justifying their hyper-protection. The danger of infection has highlighted the role of telemedicine. Internet-based video communication may ensure full care for chro­nic patients. Those methods favour bes­­ted patients with higher education. Epilepsy does not increase directly the risk of infection, but its comorbidities may worsen the course of the disease. Brain lesions and hypoxia, stress, insomnia and fever joining the infection increase seizure susceptibility. Because the danger of infection ma­de telemedicine an essential tool of pa­tient care, education and better computer supply for those in need is crucial. ]